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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of a cAMP derivative (N6, O2-dibutyryl cyclic adenosine 3',5'-monophosphate: dBcAMP) on the cell cycle and on the synthesis of typical extracellular matrix (ECM) components, i.e. collagen and glycosaminoglycans (GAG), was studied in two hormone-responsive human breast cancer cell lines VHB-1 and MCF-7. The data showed that dBcAMP induced a decrease in the proportion of cells in S + G2 + M phases due to an increase of the non-cycling (G0 phase) cell number as revealed by the Ki-67 antigen immunocytochemical study. The collagen synthesis, estimated by [3H] proline incorporation into the cellular proteins followed by an enzymatic digestion with highly purified bacterial collagenase, was not modified by dBcAMP. In contrast, the GAG synthesis, analysed by [3H] glucosamine incorporation, was increased two-fold in the dBcAMP treated cells. As a comparison we also tested 4-hydroxy-Tamoxifen (4-OH-Tam) since it induces similar cell cycle perturbations as dBcAMP. However, we did not observe a stimulation of the GAG synthesis following 4-OH-Tam treatment. These data demonstrated that the increased GAG synthesis is due to cAMP and is not a consequence of perturbations in the cell cycle. We can therefore assume that the ECM modifications induced by dBcAMP may contribute to the growth inhibition of the hormone-responsive human breast cancer cells.
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PMID:cAMP effect on extracellular matrix synthesis in human breast cancer cells. 133 23

In a worldwide collaboration, information was sought and centrally checked on mortality and recurrence for each woman in any randomised trial that began before 1985 of any aspect of systemic adjuvant therapy for early breast cancer. Checked data were available for 75,000 women (about 90% of those ever randomised), of whom 32% had died and another 10% had experienced recurrence. The parts now reviewed include 30,000 women in tamoxifen trials, 3000 in ovarian ablation trials, 11,000 in polychemotherapy trials, 15,000 in other chemotherapy comparisons, and 6000 in immunotherapy trials. Highly significant reductions in the annual rates both of recurrence and of death are produced by tamoxifen (25% SD 2 recurrence and 17% SD 2 mortality: 2p less than 0.00001), by ablation below age 50 (26% SD 6 recurrence and 25% SD 7 mortality: 2p = 0.0004), and by polychemotherapy (28% SD 3 recurrence and 16% SD 3 mortality: 2p less than 0.00001), but not by ablation at older ages or by immunotherapy. (Tamoxifen also reduced the risk of development of contralateral breast cancer by 39% SD 9: 1p less than 0.00001). For tamoxifen and for polychemotherapy the avoidance of recurrence is chiefly during years 0-4 (this difference being maintained but not increased afterwards), but the avoidance of mortality is highly significant both during and after years 0-4, so the cumulative differences in survival produced by these relatively brief treatments (median: 2 years tamoxifen, 1 year polychemotherapy) are larger at 10 than at 5 years. There is little information beyond year 10 (except for ovarian ablation, which produces separately significant mortality reductions both during and after years 0-9). Both direct and indirect randomised comparisons show long-term polychemotherapy (eg, 12 months) to be no better than shorter (eg, 6 months) regimens, but do show polychemotherapy to be significantly better than single-agent chemotherapy. Indirect randomised comparisons do not reveal significant differences between different forms of polychemotherapy, or differences between different tamoxifen doses, but do show that long-term tamoxifen (eg, 2 years, or even 5 years) is significantly more effective than shorter tamoxifen regimens. In old age (70+) tamoxifen is of demonstrated efficacy, but chemotherapy has not been evaluated. Between ages 50 and 69 direct comparisons show that chemotherapy plus tamoxifen is better (1p less than 0.00001) than chemotherapy alone both for recurrence and for mortality, and better (1p less than 0.00001) than tamoxifen alone for recurrence.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy. 133 randomised trials involving 31,000 recurrences and 24,000 deaths among 75,000 women. Early Breast Cancer Trialists' Collaborative Group. 1457 97

Expression of the c-erbB-2 proto-oncogene is inhibited by oestrogens in oestrogen-responsive human breast cancer cells, at both mRNA and protein level. Here we report that, where the regulation of c-erbB-2 is concerned, tamoxifen displays a full anti-oestrogenic activity, enhancing the expression of c-erbB-2 in oestrogen receptor-positive cells cultured with untreated fetal calf serum or reversing the inhibitory effect of added oestrogens. Meanwhile, tamoxifen strongly inhibited cell growth. Tamoxifen was inactive on both c-erbB-2 expression and growth of oestrogen receptor-negative cells. These results may have important implications to explain occasional failure of tamoxifen therapy in oestrogen receptor-positive breast cancers.
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PMID:Tamoxifen up-regulates c-erbB-2 expression in oestrogen-responsive breast cancer cells in vitro. 135 Apr 52

Tamoxifen, a partial competitive antagonist to the estrogen receptor, is a potent inhibitor of the proliferation of experimental mammary carcinoma in the rat and is widely used clinically in the treatment of breast cancer. Blockade of estrogen receptors present on neoplastic cells represents the classic mechanism of action of tamoxifen, but the drug has a variety of other actions that may contribute to its antiproliferative properties. While it is recognized that estrogens play an important role in modulating pulsatile GH release, the effect of antagonists to sex steroid receptors on GH secretory dynamics has not previously been described. In the present study we examined the effect of tamoxifen on pulsatile GH secretion in free-moving adult male and female rats. The drug, when administered in a manner previously shown to be associated with antineoplastic activity, caused a marked suppression of the amplitude of spontaneous GH secretory bursts and significantly reduced mean 6-h plasma GH levels in both sexes compared to those in their respective peanut oil-injected controls. Inhibition of spontaneous GH pulses persisted for up to 7 weeks after tamoxifen administration in both sexes. Immunoneutralization of endogenous somatostatin in tamoxifen-treated male rats completely restored both GH pulse amplitude (121.6 +/- 9.5 vs. 62.5 +/- 13.5 ng/ml in tamoxifen-treated rats given normal sheep serum; P less than 0.02) and mean 6-h plasma GH levels (53.3 +/- 6.6 vs. 17.9 +/- 3.6 ng/ml in normal sheep serum-treated rats; P less than 0.01) to levels observed in our peanut oil-injected controls. These results demonstrate that 1) tamoxifen has potent inhibitory effects on pulsatile GH secretion; and 2) the blunting of GH pulse amplitude by tamoxifen is mediated at least in part by increased release of endogenous somatostatin. These findings motivate further investigation of the clinical significance of tamoxifen-induced suppression of GH secretion in relation to the antineoplastic activity of this commonly used drug.
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PMID:Tamoxifen attenuates pulsatile growth hormone secretion: mediation in part by somatostatin. 135 Jul 60

There is now strong evidence to suggest that insulin-like growth factor I (IGF-I) plays an important role in breast cancer proliferation. Recently we observed that tamoxifen-treated stage I breast cancer patients have serum IGF-I levels significantly lower than placebo-treated patients. Since IGF-I is growth hormone (GH) dependent, we have tested the hypothesis that tamoxifen alters serum IGF-I levels through direct inhibition of GH secretion. Immature lamb pituitary cultures were examined for acute (3 h) or chronic (1-6 day) effects of the drug, using doses (0.1-10 mumol/l) based on known steady state levels in patients on tamoxifen therapy (0.31-3.1 mumol/l). Tamoxifen had a direct, dose-related, inhibitory effect on GH release from pituitary somatotropes, during acute as well as chronic treatment. The 10 mumol/l dose consistently decreased both basal and growth hormone releasing factor stimulated GH release. These in vitro data are consistent with our hypothesis that tamoxifen suppresses serum IGF-I levels by acting at the pituitary to inhibit GH release.
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PMID:Direct effects of tamoxifen on growth hormone secretion by pituitary cells in vitro. 135 80

Plasma levels of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein I (IGFBP-I) were measured in fasting blood samples obtained from 16 postmenopausal breast cancer patients before and during tamoxifen treatment for 1 to 6 months. Tamoxifen suppressed total plasma IGF-I by a mean of 28.5% (P less than 0.001) but elevated plasma IGFBP-I by a mean value of 78% (P less than 0.001). Changes in plasma levels of growth hormone, insulin, or insulin C-peptide were not observed. These findings suggest that tamoxifen exerts its influence on plasma IGF-I and IGFBP-I by mechanisms other than those known to regulate the plasma levels of these peptides, primarily growth hormone and insulin, respectively. A dual effect suppressing plasma IGF-I and elevating plasma IGFBP-I suggests that tamoxifen may have a significant influence on endocrine and possibly paracrine delivery of IGF-I to breast cancer cells in vivo.
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PMID:Influence of tamoxifen on plasma levels of insulin-like growth factor I and insulin-like growth factor binding protein I in breast cancer patients. 138 Aug 89

Tamoxifen treatment of women with advanced breast cancer has previously been reported to reduce plasma insulin-like growth factor-type I (IGF-I) concentrations. In this study we have examined the effect of treatment with Tamoxifen, medroxyprogesterone acetate (MPA) or 4-hydroxyandrostenedione (4-OHA) on plasma IGF-I and IGF-II concentrations. As IGF-binding proteins (IGFBPs) can modulate the biological effects of IGF-I, plasma IGFBP-I levels were also measured. Treatment with Tamoxifen for 2 weeks resulted in a small, but significant, decrease in IGF-I levels, but increase in the plasma concentration of IGFBP-I. In contrast, treatment with MPA increased levels of IGF-I, but significantly reduced plasma IGFBP-I concentrations. Treatment with 4-OHA had no significant overall effect on plasma IGF-I or IGFBP-I levels, although changes were detected for some subjects. Plasma IGF-II concentrations were not altered by treatment with Tamoxifen, MPA or 4-OHA. It is concluded that although treatment with Tamoxifen or MPA produced significant changes in plasma IGF-I concentrations, any physiological effects of such changes are likely to be modulated by the corresponding alterations in plasma IGFBP-I concentrations.
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PMID:The effect of endocrine therapy with medroxyprogesterone acetate, 4-hydroxyandrostenedione or tamoxifen on plasma concentrations of insulin-like growth factor (IGF)-I, IGF-II and IGFBP-1 in women with advanced breast cancer. 138 3

Mast cells have been studied extensively for their involvement in allergic reactions, where they secrete numerous powerful mediators in response to immunoglobulin E and specific antigens. However, they are also triggered by neuropeptides, they have been found in close contact with neurons, and they are activated in diseases such as angioedema, interstitial cystitis and irritable bowel disease, the prevalence of which is much higher in women. When tested on purified rat peritoneal mast cells, 17 beta-estradiol augmented secretion of histamine and serotonin, starting at 1 microM and in a dose-dependent manner, whether stimulated by the mast cell secretagogue compound 48/80 or the neuropeptide substance P. However, 17 beta-estradiol did not augment mast cell secretion stimulated by immunoglobulin E and specific antiserum indicating that immunologic stimulation is under different regulation. Testosterone inhibited secretion induced by compound 48/80. Tamoxifen, an estrogen receptor antagonist used in the treatment of breast cancer, inhibited serotonin and histamine release from purified rat peritoneal mast cells triggered by compound 48/80 or substance P. Tamoxifen also inhibited the increase in intracellular free Ca2+ originating from an influx of extracellular Ca2+ in response to compound 48/80. Moreover, tamoxifen antagonized the synergistic effect of phorbol myristate and the cation ionophore A23187 on mast cell secretion, suggesting that tamoxifen's inhibition may be due to regulation of protein kinase C activity. Tamoxifen may, therefore, have a beneficial effect in other neuroimmunoendocrine disorders both through estrogen receptor blockade and inhibition of mast cell secretion.
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PMID:Estradiol augments while tamoxifen inhibits rat mast cell secretion. 138 69

A case with lower extremity phlebothrombosis and pulmonary embolism caused by progesterone is reported in this paper. The patient is a 64-year-old woman who had been operated on for right breast cancer 22 years before. It was noticed that there was a relapsing cancer on her right shoulder 6 months before this episode. After effective treatment of 5-FU, she had received 1,200mg of Medroxyprogesterone acetate and 30mg of Tamoxifen daily for 4 months. With the complaint of dyspnea and left leg swelling 4 months after above treatment, she was admitted in our hospital. Laboratory data and angiograms showed venous thrombosis in her left leg and pulmonary embolism. Relapsing cancer had already disappeared by the time she was admitted. After discontinuance of these medicines, her condition had improved. Considering these observations, the patient's phlebothrombosis and embolism seem to have been caused by Medroxyprogesterone acetate.
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PMID:[A case of phlebothrombosis of lower extremity and pulmonary embolism due to progesterone]. 138 85

82 women who had had surgery for removal of breast cancer were randomised during the primary care period before initiation of any chemotherapy or radiotherapy into two groups: no drug treatment (n = 40) and 20 mg tamoxifen per day for 2 years (n = 42). Mononuclear leucocyte (MNL) fractions from blood samples were collected during the first 368 days of the study and ADP-ribosylation was quantified. Tamoxifen treatment resulted in a dose-duration increase in ADP-ribosylation. This was true even after adjustment for covariates such as age, smoking habits, oestrogen use, menstruation and tumour size. These data suggest that part of the antitumour effects of tamoxifen treatment in vivo relates to an enhanced immune cell responsiveness, as indicated by the increased MNL ADP-ribosylation.
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PMID:Elevation of ADP-ribosylation as an indicator of mononuclear leucocyte responsiveness in breast cancer patients treated with tamoxifen. 138 13


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